The antibiotic known as "primycin" has first been described in the Hungarian patent specification No. 153,539; it was extracted as a native antibiotic from the product of a fermentation carried out with the culture of Thermopolyspora galeriensis fungal strain. Primycin mainly acts on gram-positive cocci, is not absorbable and is useful for a topical treatment. The preparation of primycin has been published in J. Chem. Soc. Perkin I 1984, 816 wherein primycin was characterized by a single formula. However, it is now known that this substance is a mixture consisting of several components (cf. the Hungarian patent specifications Nos. 195,514 and 196,425). Although primycin is a very effective antibiotic, its therapeutical utilization was made extraordinarily difficult since it is practically insoluble either in water or in physiologically acceptable solvents. Thus, several efforts had earlier been made to eliminate these difficulties and to prepare pharmaceutical compositions containing primycin in a therapeutically well utilizable form while maintaining its efficiency as a whole.
Thus, the preparation of a semisolid composition containing primycin as a heterocolloid in 50% aqueous ethanol was suggested in the Hungarian patent specification No. 173,708. However, by using this process, a gel containing at most 0.2% of primycin can be prepared with the further disadvantage that a burning pain sensation on the damaged skin surface is elicited. This problem is avoided by adding a local anesthetic agent to the composition whereby an allergic response can be evoked in the patient. A further disadvantage consists in that skin damage can occur by a long-lasting treatment with such a composition as it has been proved by animal experiments carried out on New Zealand rabbits.
A composition containing the complex of primycin sulfate with N-methyl-pyrrolidone in a predetermined weight ratio and suggested in the Hungarian patent specification No. 194,493 proved to be preferred. This composition having a gel consistency is useful to incorporate the active ingredient in a micro-distribution practically in all galenic forms such as ointments, creams, foams, dusting powders and the like, however, it is not useful to prepare transparent solutions.
There exists, however, an area of dermatology which demands an antibiotic treatment, i.e. the skin disease caused by Propionibacterium acne, the various types of which are usually treated by painting with alcoholic solutions of antibiotics namely, both the patient and the disease require the cleaning and drying effects of alcohol. Since this treatment does not involve any durable exposition (as opposed to the semisolid heterocolloid containing alcohol), this painting with an alcoholic solution can be used without any danger.
For alcoholic paintings, antibiotics with a tetracycline--skeleton as well as erythromycins had been used for a long time; however, most pathogens became resistant to these antibiotics. Due to its very high price, the use of clindamycin, introduced in recent years, has not become wide-spread.
The aqueous alcohol-based compositions of this kind known up to the present usually contain about 50% of alcohol and 1 to 1.5% by mass of antibiotic dissolved therein such as Staticin 1.5 topical solution (Physicians' Desk Reference 40, Ed. Medical E. Comp. USA 1986).
Primycin which destroys in a concentration as low as 10.sup.-7 g/ml both the Propionibacterium acne as well as Staphylococcus bacteria, being present as co-pathogens, would be considered to be an ideal antibiotic for the topical therapy of acne if a solution of at least 1% concentration could be prepared from it. However, such a solution could not until now be prepared from primycin since primycin sulfate dissolves up to 0.2% as a maximum in ethanol or propanol. This problem is solved by the process according to the present invention which overcomes any difficulty in obtaining a solution containing primycin in a concentration of even 1.5% by mass.